Genetic analysis of indel markers in three loci associated with Parkinson's disease

<div><p>The causal mutations and genetic polymorphisms associated with susceptibility to Parkinson’s disease (PD) have been extensively described. To explore the potential contribution of insertion (I)/deletion (D) polymorphisms (indels) to the risk of PD in a Chinese population, we performed genetic analyses of indel loci in <i>ACE</i>, <i>DJ-1</i>, and <i>GIGYF2</i> genes. Genomic DNA was extracted from venous blood of 348 PD patients and 325 age- and sex-matched controls without neurodegenerative disease. Genotyping of the indel loci was performed by fragment length analysis after PCR and DNA sequencing. Our results showed a statistically significant association for both allele <i>X</i> (alleles without <i>5</i>) vs. <i>5</i> (odds ratio = 1.378, 95% confidence interval = 1.112–1.708, <i>P</i> = 0.003) and genotype <i>5/X+X/X</i> vs. <i>5/5</i> (odds ratio = 1.681, 95% confidence interval = 1.174–2.407, <i>P</i> = 0.004) in the <i>GIGYF2</i> locus; however, no significant differences were detected for the <i>ACE</i> and <i>DJ-1</i> indels. After stratification by gender, no significant differences were observed in any indels. These results indicate that the <i>GIGYF2</i> indel may be associated with increased risk of PD in northern China.</p></div

Association study on indel locus of <i>GIGYF2</i> by gender stratification.

<p>Association study on indel locus of <i>GIGYF2</i> by gender stratification.</p

Nine allelic sequences were identified in the <i>GIGYF2</i> locus in this study.

<p>A6 (27.6%) is used as a reference sequence. Compared with A6, A5 (47.0%) and A7 (24.4%) were 3-bp repeated indels, and the others indels were different structural variations enclosing the poly-Q core unit (approximately 1.2%). The upper sequence represents base pairs of nucleic acids, and the lower sequence represents the corresponding amino acids.</p

The information of indel loci and PCR parameters.

<p>The information of indel loci and PCR parameters.</p

Association study on indel locus of <i>GIGYF2</i> by genotypic and allelic stratification.

<p>Association study on indel locus of <i>GIGYF2</i> by genotypic and allelic stratification.</p

Frequency distribution and association analysis on indel locus of <i>GIGYF2</i> gene.

<p>Frequency distribution and association analysis on indel locus of <i>GIGYF2</i> gene.</p

Comparison of <i>GIGYF2</i> indel locus between male and female.

<p>Comparison of <i>GIGYF2</i> indel locus between male and female.</p